alteplase
Thrombolytic· Brands: Actilyse, ActivaseIV
Mechanism of action
Alteplase is a recombinant tissue plasminogen activator. It binds to fibrin in a thrombus and converts plasminogen to plasmin. Plasmin degrades the fibrin matrix, leading to clot lysis. It has low affinity for circulating plasminogen, limiting systemic fibrinolysis.
Pharmacokinetics
Alteplase is given intravenously. It is rapidly cleared from the body, with an initial half-life of about 5 minutes and a terminal half-life of approximately 40 minutes. It is metabolised in the liver and removed by the reticuloendothelial system. Its effect on fibrinogen and other clotting factors may persist for up to 24 hours.
Indications & dosing
Acute ischaemic stroke
Max 90 mg. Give 10% as IV bolus over 1 min, then remainder over 60 min.
- adult · IV: 0.9 mg/kg once · Max 90 mg. Give 10% as IV bolus over 1 min, then remainder over 60 min.
Acute ST-elevation myocardial infarction (STEMI)
Accelerated regimen: 15 mg IV bolus, then 50 mg over 30 min, then 35 mg over 60 min.
- adult · IV: 100 mg once · Accelerated regimen: 15 mg IV bolus, then 50 mg over 30 min, then 35 mg over 60 min.
Pulmonary embolism (PE)
Administer as continuous infusion over 2 hours.
- adult · IV: 100 mg once · Administer as continuous infusion over 2 hours.
Catheter occlusion (off-label)off-label
Instill 2 mg into occluded catheter lumen; dwell for 30-120 min, then aspirate.
- adult · IV: 2 mg once per occlusion · Instill 2 mg into occluded catheter lumen; dwell for 30-120 min, then aspirate.
Contraindications & precautions
- Active internal bleeding · Alteplase is contraindicated in the presence of active bleeding.
- History of intracranial haemorrhage · Risk of recurrence is high.
- Recent intracranial surgery or severe head trauma · Within 3 months for stroke patients.
- Severe uncontrolled hypertension · Systolic >185 mmHg or diastolic >110 mmHg despite treatment.
- Known bleeding diathesis · Includes coagulopathies, platelet disorders, or anticoagulant use with elevated INR.
- Pregnancy · Use only if benefit outweighs risk; risk of bleeding in mother and fetus.
- Recent major surgery or trauma · Within 10 days; risk of surgical site bleeding.
- Concurrent warfarin therapy (INR >1.7) · Increased bleeding risk; consider reversal before thrombolysis.
- Monitor closely for signs of bleeding, including intracranial and internal bleeding, during and after administration.
- Ensure blood pressure is adequately controlled before administration (e.g., below 185/110 mmHg for ischaemic stroke).
- Avoid invasive procedures, arterial punctures, and intramuscular injections during therapy.
- Have resuscitation equipment and blood transfusion facilities available in case of serious bleeding.
Adverse effects
- Intracranial haemorrhageserious
- Major systemic bleedingserious
- Minor bleeding (e.g., gingival, epistaxis)
- Angioedemaserious
- Hypotension
- Anaphylaxisserious
Renal & hepatic adjustment
- Hepatic impairment (severe): Use with caution; no specific dose adjustment recommended. Increased risk of haemorrhage.
Monitoring, pregnancy & toxicity
- Blood pressure · During and after infusion
- Neurological status · Frequently during and after infusion in stroke patients
- Signs of bleeding · Continuous observation
- Heart rate and rhythm · During infusion
- Signs of anaphylaxis · During infusion
- Pregnancy: Use only if the potential benefit outweighs the risk to the fetus, particularly for life-threatening conditions. Alteplase should be avoided in pregnancy unless there is a clear indication, due to the risk of haemorrhage affecting both mother and fetus.
- Toxicity: Haemorrhage · Stop alteplase infusion; provide supportive care. For severe bleeding, consider cryoprecipitate, fresh frozen plasma, or tranexamic acid. If heparin is administered, consider protamine sulfate.
- Toxicity: Anaphylactoid reaction · Discontinue infusion; administer antihistamines, corticosteroids, and epinephrine if indicated.
Clinical notes
Alteplase is used for thrombolysis in acute ischaemic stroke, acute myocardial infarction, and massive pulmonary embolism with haemodynamic compromise. In stroke, it must be given within 4.5 hours of symptom onset. Blood pressure must be controlled to <185/110 mmHg before administration. Bleeding is the major adverse effect; risk factors include recent surgery, trauma, and active bleeding. It is contraindicated in patients with a history of intracranial haemorrhage, uncontrolled hypertension, or recent anticoagulant use. Administer according to local thrombolysis protocols, and monitor for signs of haemorrhage, especially intracranial bleeding. Have reversal agents available, but alteplase has no specific antagonist.
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BNF; local formulary